The FDA approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for patients with multiple myeloma who have received at least one prior therapy.
The approval was based on the results of two randomized, open-label trials. The CASTOR trial evaluated daratumumab in combination with bortezomib and dexamethasone compared with bortezomib and dexamethasone alone. Adding daratumumab to treatment resulted in a 61 percent reduction in the risk of disease progression or death (HR=0.39; 95% CI 0.28-0.53; p<0.0001); the median PFS was not reached in the daratumumab combination cohort, compared with 7.2 months in the bortezomib and dexamethasone alone cohort. The addition of daratumumab also resulted in an increased ORR: 83 percent versus 63 percent (p<0.0001).
The most common treatment-related AEs in the CASTOR trial included infusion-related reactions (IRRs), diarrhea, peripheral edema, upper respiratory tract infection, peripheral sensory neuropathy, cough, and dyspnea.
The POLLUX trial evaluated daratumumab in combination with lenalidomide and dexamethasone compared with lenalidomide and dexamethasone. The daratumumab combination therapy resulted in a 63 percent reduction in the risk of disease progression or death compared with lenalidomide and dexamethasone alone (HR=0.37; 95% CI 0.27-0.52; p<0.0001); the median PFS was not reached in the daratumumab combination cohort compared with 18.4 months for those who received lenalidomide and dexamethasone alone. The addition of daratumumab also significantly increased ORR: 93 percent versus 76 percent (p<0.0001).
The most common treatment-related AEs in the POLLUX trial included IRRs, diarrhea, nausea, fatigue, pyrexia, upper respiratory tract infection, muscle spasm, cough, and dyspnea.
Daratumumab carries a warning for neutropenia and thrombocytopenia.
Source: Janssen press release, November 21, 2016.